|Year : 2012 | Volume
| Issue : 4 | Page : 404-411
Factors associated with high prevalence of pulmonary tuberculosis in HIV-infected people visiting for assessment of eligibility for highly active antiretroviral therapy in Kathmandu, Nepal
Bishnu R Tiwari1, Surendra Karki2, Prakash Ghimire3, Bimala Sharma4, Sarala Malla5
1 School of Health and Allied Sciences, Pokhara University, Kaski, Nepal
2 Department of Epidemiology and Preventive Medicine, Infectious Disease Epidemiology Unit, Monash University, Melbourne, Australia
3 Central Department of Microbiology, Tribhuvan University, Kathmandu, Nepal
4 Institute of Medicine, Department of Public Health, Tribhuvan University, Kathmandu, Nepal
5 National Public Health Laboratory, Kathmandu, Nepal
|Date of Web Publication||25-May-2017|
Department of Epidemiology and Preventive Medicine, Infectious Disease Epidemiology Unit, Monash University, Melbourne
Background: Tuberculosis is the leading cause of deaths among HIV patients. In this study, we estimated the prevalence of pulmonary tuberculosis (PTB) and identified the factors/co-morbidities associated with active PTB in HIV-infected people visiting the national public health laboratory to assess their eligibility to receive highly active antiretroviral therapy.
Methods: A cross-sectional study was conducted to measure the prevalence of pulmonary tuberculosis. Data on probable risk factors in patients with and without PTB were compared, calculating the odds ratio as a measure of association. Factors showing significant association in univariate analyses were included in a stepwise backward logistic regression model to adjust for confounding.
Results: The prevalence of pulmonary tuberculosis was 32.4 % (95% confidence interval (CI) 30.25–34.56). In the univariate analysis, patients with PTB were more likely to be older, married, and have a longer duration since the diagnosis of HIV, diarrhoea, parasitic infection, lower CD4 T-cell counts, and lower CD4/CD8 ratio. However, the backward stepwise logistic regression revealed that only the CD4 T-cell count < 200/μL (AOR 11.69, 95% CI 6.23–21.94), CD4 T-cell count 200–350/μL (AOR 2.52, 95% CI 1.30–4.89), diarrhoea (AOR 2.77, 95% CI 1.78–4.31), parasitic infection (AOR 3.34, 95% CI 2.02–5.50) and ‘sex with partner’ as probable modes of transmission (AOR 0.44, 95% CI 0.20–0.93) were independently associated with pulmonary tuberculosis.
Conclusion: A high prevalence of pulmonary tuberculosis was observed. Participants with tuberculosis were significantly more likely to have lower CD4 counts, diarrhoea, and parasitic infections. HIV treatment programmes should consider these factors for better outcomes.
Keywords: HIV, CD4, pulmonary tuberculosis, diarrhoea, Nepal
|How to cite this article:|
Tiwari BR, Karki S, Ghimire P, Sharma B, Malla S. Factors associated with high prevalence of pulmonary tuberculosis in HIV-infected people visiting for assessment of eligibility for highly active antiretroviral therapy in Kathmandu, Nepal. WHO South-East Asia J Public Health 2012;1:404-11
|How to cite this URL:|
Tiwari BR, Karki S, Ghimire P, Sharma B, Malla S. Factors associated with high prevalence of pulmonary tuberculosis in HIV-infected people visiting for assessment of eligibility for highly active antiretroviral therapy in Kathmandu, Nepal. WHO South-East Asia J Public Health [serial online] 2012 [cited 2019 Jul 19];1:404-11. Available from: http://www.who-seajph.org/text.asp?2012/1/4/404/207042
| Background|| |
Tuberculosis (TB) is caused by bacteria belonging to Mycobacterium tuberculosis complex. About one third of the world’s population is latently infected with TB bacteria. HIV infection leads to immune deterioration, thus providing a platform for the activation of latently infected TB.
TB is the leading cause of deaths in HIV-infected people in resource-limited settings. About one third of HIV-infected people are co-infected with TB, most of them living in low-and middle-income countries. In Nepal, 80 000 people have active TB infection at any one time, with about 40 000 new cases and 5000–7000 deaths per year. As many as 11% of newly detected TB cases are infected with HIV and up to 23% of newly detected HIV cases are co-infected with TB., A high prevalence of HIV/TB co-infection is described elsewhere.,,,
Estimating the magnitude of pulmonary tuberculosis (PTB), and the factors associated with it in HIV-infected people, may be useful at policy level as well as for management of individual patients for better outcomes. In resource-limited settings, HIV is often diagnosed in late stage of the disease and in association with other co-morbidities related to deterioration of the immune system. In this study, we aimed to estimate the prevalence of PTB and identify the factors associated with it in HIV-infected people visiting the national public health laboratory (NPHL) for assessing eligibility to highly active antiretroviral therapy (HAART).
| Methods|| |
Setting and study population
This study was conducted in people infected with HIV, attending NPHL for CD4 T-cell count in Kathmandu, Nepal, primarily for the purpose of assessing their eligibility for HAART. NPHL is the largest referral centre in the country, equipped with an automated CD4 T-cell count facility. Although the facility is located in the capital city, the participants came from various parts of the country as a CD4 T-cell count service was not available outside of Kathmandu until the middle of 2008. Nepal is a landlocked country in South Asia with a poorly functioning health system. During our study period, the country had widespread and violent civil war and high political instability.
Study design and data collection
We conducted a cross-sectional study to measure the proportion of active pulmonary tuberculosis and analysed the data comparing patients with PTB and without PTB, to identify the associated factors/co-morbidities. A total of 1807 participants were included in the study from March 2005 to December 2008. The median age of participants was 30 years (interquartile range, 25–35 years), 66% of whom were male, and 90% were married. The study was explained to participants, who were assured about the confidentiality and anonymity of the collected information. An informed verbal consent was obtained from all the volunteers.
Definition of study variables
Pulmonary tuberculosis was defined as a participant whose sputum specimen was positive for acid fast bacilli (AFB) by microscopic examination at NPHL; or who had a prior medical record of being diagnosed with PTB on the basis of other laboratory investigations (sputum smear examination or microbiological culture) from other health-care facilities. Participants with tuberculosis other than PTB were excluded from the study. Participants with pulmonary tuberculosis already receiving HAART were also excluded from the analysis. The status of diarrhoea was ascertained by self-reporting of participants having loose stools 3 or more times a day. Information on parasitic infection was collected from the examination of stool specimens from a random subset of the study sample. Information about age, sex, possible mode of transmission, and date of HIV diagnosis was collected from a patient register maintained at NPHL.
The volunteers were instructed on appropriate sputum specimen collection. Briefly, all sputum smears were stained with gram stain and observed under low power (10×) objective. Samples having less than 10 epithelial cells and more than 25 pus cells per low-power field were accepted and those not meeting the criteria were requested to submit a repeat sample. Sputum specimens collected and stained following AFB staining methods were examined microscopically following the standard protocol. At least 200 fields were evaluated before reporting negative.
Microscopic examination of stool samples was performed by wet mount, formal-ether sedimentation technique and modified acid fast staining. Three millilitres of blood from each participant was collected for CD4 T-cell count, performed using flow cytometry.
Data were entered in a Microsoft Excel spreadsheet and statistical analysis was performed by STATA (version 10; StataCorp, College Station, United States of America). The measure of association between different explanatory variables and TB infection (outcome variable) was expressed in terms of odds ratio (OR) with corresponding 95% confidence interval. Factors significantly associated with TB infection at p<0.05 in univariate analysis were adjusted for confounders in a backward stepwise multiple logistic regression model. The independently associated variables were tested for statistical interaction by using a test of homogeneity. The chi-square test was used to test statistical significance in categorical variables and the Wilcoxon ranksum test was used for continuous variables. A p-value of < 0.05 was considered statistically significant.
| Ethics|| |
The study was approved by the Ethics Committee of Tribhuvan University, Kathmandu. Participation was fully voluntary based oninformed verbal consent. Participants diagnosed with TB or being infected with intestinal parasites were referred appropriately for treatment.
| Results|| |
The median time since the first diagnosis of HIV was 23 weeks (inter-quartile range, 7–36 weeks). The major modes of transmission reported were injecting drug use (41.2%) and commercial sex (36.6%). The median CD4 and CD8 T-cell count was 257/μL (inter-quartile range, 132–419) and 1010/μL (inter-quartile range, 657–1432), respectively. About 86% of the participants had a CD4/CD8 cell ratio of ≤0.5.
Of the 1807 participants, 32.4% (95% CI, 30.25–34.56) were ascertained to have pulmonary tuberculosis infection. The proportion of TB was not significantly different among males (33.8%) and females (29.5%). Among patients with PTB, 82.7% had a CD4 T-cell count of less than < 200/μL and 73.9% had a CD4/CD8 T-cell ratio of < 0.25. In the univariate analysis, patients with PTB were more likely to be older, married, and have a longer duration since the diagnosis of HIV, diarrhoea, parasitic co-infection, lower CD4T-cell count, and lower CD4/CD8 ratio. The distribution of factors across patients with and without PTB, and the measure of association in terms of corresponding unadjusted odds ratios, are shown in [Table 1].
All the factors significantly associated with PTB in univariate analysis were included in the multiple logistic regression model. The backward stepwise logistic regression revealed that only the CD4 T-cell counts of < 200/μL and 200–350/μL, diarrhoea, parasitic infection and sex with partner as probable mode of transmission were independently associated. Participants with PTB were about 12 times more likely to have a CD4 T-cell count of < 200/μL and two-and-a-half times more likely to have a CD4 T-cell count of 200–350/μL compared with participants with a CD4 count of > 350/μL. Similarly, participants with TB were more than twice as likely to have diarrhoea and parasitic infection/infestation. However, participants with probable mode of transmission by “sex with partner” were significantly less likely to have active TB infection. The corresponding adjusted OR from multivariate analysis is shown in [Table 2].
|Table 2: Factors associated with tuberculosis infection (multivariate analysis)|
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| Discussion|| |
This is the largest study in the country to date involving participants from different risk groups to estimate the prevalence of PTB and associated factors and co-morbidities in HIV-infected people before the start of HAART. Our study revealed that about one third of the participants presenting at NPHL had a pulmonary tuberculosis infection, which suggests an alarming PTB epidemic among HIV-infected people in Nepal. Our finding is very high compared with similar studies done in Cambodia and the United Republic of Tanzania,,, although the Cambodian study involved active case-finding of TB in a home-care programme of HIV-infected people. It should be noted that in our study, cases of PTB included newly diagnosed as well as existing TB cases that had not commenced HAART. This may partly explain the higher prevalence observed in our study. Also, since our study participants were being assessed for HAART eligibility on the basis of CD4 T-cell count, it is clear that at least one third of HIV patients had already developed PTB before the start of HAART. Such a high TB burden adds complexity to HIV treatment as well as to treatment of TB itself., In addition, the finding has implications for the possible impact of HIV on a TB epidemic:since patients were diagnosed by positive sputum smear microscopy, it is probable that they are highly infectious and a powerful source of transmission to others in their close environment, particularly their families. Although it has been shown that patients with CD4 T-cell counts of < 200/μL may be less infectious, representing a lower risk of transmission,HIV-infected TB patients can be highly infectious in case of multi-drug resistant tuberculosis.
This study showed that the HIV-infected people attending for a CD4 T-cell count already had a very poor immune status. The median CD4 count was 257/μL and about 86% of all participants had a CD4/CD8 ratio of ≤ 0.5. The fact that the median time since the diagnosis of HIV was less than six months indicates that the participants were diagnosed in late stages of the disease, which is not uncommon in resource-limited settings.
The lower CD4 count was strongly associated with the higher odds of PTB. This finding suggests the extent of missed opportunity of preventing TB, probably due to a delayed start of HAART; earlier initiation, at a CD4 count of >350/μL, may have a significant effect on reducing the incidence of TB. Lower CD4 count is a well-established risk factor for development of active TB among HIV-infected people.,, The guideline of the World Health Organization to initiate HAART at CD4 T-cell count ≤ 350/μL should therefore be followed strictly to prevent TB or other opportunistic infections.
The study showed diarrhoea and intestinal parasitic infections to be important co-morbidities among participants with pulmonary tuberculosis. Participants with TB had more than twice the odds of having diarrhoea after adjustment for other possible confounders. It is not entirely clear how diarrhoea is related to a TB outcome; however a randomized controlled trial from Zambia has demonstrated that preventive TB treatment can also prevent diarrhoea among HIV-infected patients. It is very important to investigate further the relationship between diarrhoea and active TB in HIV-infected patients. Similarly, participants with TB had more than three times higher odds of having an intestinal parasitic infection. Opportunistic intestinal parasitic infections are common in late stage HIV disease, and have been described elsewhere. Given the high proportion of participants in our study with diarrhoea and/or intestinal parasitic infection, it is likely that the prevalence of under-nutrition may also be very high. Although we did not test for under-nutrition, a study from the United Republic of Tanzania has shown 70% prevalence of malnutrition in HIV/TB co-infected patients.
When ‘sex with partner’ was a possible mode of transmission, the odds of TB status were almost halved. This is plausible because, compared with participants whose potential mode of transmission was injection drug use or commercial sex, those with ‘sex with partner’ as mode of transmission were married females (87%), probably housewives, who may be considered less vulnerable to TB. However, supplementary data are lacking to support this proposition.
One limitation of the study was that the PTB status in most of the participants was ascertained on the basis of sputum smear microscopy. Microscopy is a less sensitive method than culture when the bacterial load in the sputum is lower. The prevalence of PTB may therefore be marginally underestimated. In addition, we do not have data on the status of anti-tuberculosis treatment or its duration. In the scenario of treatment of TB for more than 3–4 weeks, the patient may convert to smear negative, thus leading to a further underestimation of true prevalence. Since the study was of cross-sectional nature, we have no information on the temporal relationship between diarrhoea and parasitic infection with active PTB; these variables should therefore be considered as co-morbidities rather than any indication of risk of developing TB. Data on possible modes of transmission are based on patient information. However, one of the strengths of our study is that it is based on real world observed settings.
| Conclusions|| |
We conclude that the prevalence of pulmonary tuberculosis is alarmingly high in our study population. The majority of participants had a very poor immune status as assessed on the basis of the CD4/CD8 ratio before the initiation of HAART. The odds of PTBs were higher in participants with lower CD4 T-cell counts, diarrhoea, and intestinal parasitic infection. These findings may be useful for formulating better strategies for HIV and TB treatment programmes in the country. For example, early diagnosis of HIV infection; motivation of patients to visit CD4 T-cell count facilities as early as possible; initiation of HAART on higher threshold values of CD4 T-cell counts; and treatment of intestinal parasitic infection as an integral part of HIV programmes, may prove beneficial for better treatment outcomes.
| Acknowledgements|| |
We are thankful to all the volunteers who participated in the study, and the laboratory staff of the National Public Health Laboratory, Kathmandu, Nepal.
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[Table 1], [Table 2]